BM-MSCs promote prostate cancer progression via the conversion of normal fibroblasts to cancer-associated fibroblasts

Abstract

Recent studies have suggested that prostate cancer (PCa) is able to recruit bone marrow derived mesenchymal stem cells (BM-MSCs) to promote metastasis. The detailed mechanisms, especially the involvement of stromal cells, remain unclear. We found that the recruited BM-MSCs might be able to convert the normal fibroblasts to more cancer associated fibroblast (CAF)-like characteristics via alteration of secreted TGFβ-1. The consequences of such conversion might then enhance the PCa growth and invasion. Addition of functional TGFβ-1 or interruption with TGFβ-1 inhibitor SB431542 led to alteration of the BM-MSCs-induced CAF conversion and influence on the PCa cell growth and invasion. Together, these results suggest that BM-MSCs not only can be directly recruited by PCa epithelial cells to promote PCa invasion, they can also go through conversion of normal fibroblasts to CAFs to enhance PCa cell growth and invasion. Targeting the infiltrating BM-MSCs via either interruption of the interaction between PCa and BM-MSCs or prevention of the conversion of NFs to CAFs via inhibition of TGFβ-1 signal may result in the suppression of PCa progression.